Hippocampal glutamate is increased and associated with risky drinking in young adults with major depression

Abstract Background Risky drinking in young people is harmful, highly prevalent and often complicated by comorbid mental health problems that compound alcohol-induced impairment. The hippocampus and the glutamate system have been implicated in the pathophysiology of alcoholism and depression. This study aimed to determine whether risky drinking is associated with glutamate levels recorded within the hippocampus of young adults with major depression. Methods Sixty-three young persons with major depression (22.1±3.1 years; 65% female) and 38 healthy controls were recruited. Participants completed the alcohol use disorder identification test and underwent proton magnetic resonance spectroscopy to measure in vivo glutamate levels within the hippocampus following a period of at least 48 h of abstinence. Results Young adults with depression had significantly increased hippocampal glutamate levels and a positive association between the level of alcohol use and glutamate. Regression analysis revealed that higher levels of hippocampal glutamate were predicted by having increased levels of risky drinking and depression. Limitations Small sample sizes for testing diagnosis by risky drinking interaction and use of creatine ratios rather than the absolute concentrations of glutamate. Discussion The hippocampus is a critical region; given its role in learning and memory as well as mood regulation, and the neurochemical changes observed in this study may precede structural changes, which are commonly observed in both depression and alcohol misuse. These findings suggest that young adults with major depression who engage in risky drinking may be at increased risk of glutamate excitotoxicity.